Participation of Fos and Jun in Multistage Carcinogenesis
The discovery that transforming genes of oncogenic retroviruses are transduced variants of eucaryotic genes launched the current era of molecular carcinogenesis. Studies in animals had established that certain chemicals could cause malignant tumors, that cancer induction is a multistage process, and that carcinogenesis is organ specific in humans and other mammals. The contribution of specific genetic changes to multistage carcinogenesis has been the focus of considerable study. The chapter examines data on the c-fos and c-jun gene products in the context of multistage carcinogenesis. The concurrence of human and animal data indicates that overexpression of c-Fos contributes to the development of osteosarcomas and related bone tumors probably at an early stage of carcinogenesis. The focus of most studies relating c-Fos and c-Jun to the process of carcinogenesis involve examination of levels of expression, since experiments with v-fos and v-jun indicate that increased expression can be carcinogenic.